Proposed mechanism of action of IL-5 on IL-4–induced Ag-specific Tregs to expand Th2 cytokine–dependent Tregs of the Ts2 phenotype. Within the naive CD4⁺CD25⁺ T-cell population there are a small number of Tregs with TCR specific for Ag that can be induced to Ts2,³  by stimulation with Ag in the presence of IL-4. These Ag-specific Tregs express Il-5rα and are further expanded by IL-5, produced by maturing Th2 cells or exogenous rIL-5. Most nTregs have TCR that do not recognize the Ag in question, which are activated by IL-4 and induced to proliferate but do not differentiate to express Il-5rα. They remain as nTregs and do not mediate Ag-specific tolerance. This study showed that rIL-5 therapy enhanced expansion of Ts2 cells that had been activated by immunizing Ag and production of IL-4 by the host T cells. The Il-5rα–expressing Ag-specific Tregs were selectively expanded by rIL-5 therapy to suppress autoimmunity, including Th1 cells, Th17 cells, and macrophages.